基于GEO数据库对儿童哮喘急性发作靶基因的生物信息学分析

Bioinformatic Analysis of Target Genes in Children with Acute Asthma Attack Based on GEO Database

为了通过生物信息学技术筛选并分析关键基因以探究儿童哮喘急性发作的病理机制,从GEO数据库下载儿童哮喘急性发作相关基因芯片数据集(GSE103166),用R软件包工具筛选出哮喘急性发作患儿与健康儿童的差异表达基因(differentially expressed genes, DEGs),用DAVID (version 6.8)在线工具获取DEGs列表的GO和KEGG注释结果,同时通过STRING (version 11.0)获取其蛋白质互作数据,应用Cytoscape及其插件MCODE构建蛋白质互作网络、鉴定关键基因。结果显示,共筛选出78个DEGs,其中上调基因共49个,下调基因共29个。这些DEGs主要富集于核质转运调控、免疫系统过程调节等生物过程;核小体、DNA包装复合物等细胞组分;Rho GTP酶结合、离子型谷氨酸受体结合等分子功能。KEGG通路分析结果提示其主要富集在系统性红斑狼疮和哮喘信号通路。在这些DEGs中,筛选得到一个基因模块, GO分析显示该模块主要富集在γ干扰素介导的信号通路、通过MHCⅡ类分子进行抗原加工和外源性抗原肽的呈递、通过MHCⅡ类分子进行抗原加工和抗原肽的呈递等生物过程;MHCⅡ类蛋白复合物、内质网膜腔侧、内质网膜腔侧组成部分等细胞组分;MHCⅡ类受体活性、抗原肽结合、跨膜信号受体活性等分子功能。KEGG通路分析提示该模块主要富集在哮喘、移植物抗宿主病、同种异体排斥反应等通路。该基因模块涵盖5个关键基因,分别为HLA-DPB1、HLADQB1、HLA-DQB2、MT2A和KIF11。上述分析结果表明,文中筛选的DEGs和关键基因有助于加深对儿童哮喘急性发作病理机制的理解,其中HLA-DPB1、HLA-DQB1、HLA-DQB2等关键基因已得到相关研究的验证,未经证实的MT2A、KIF11关键基因,可能是儿童哮喘急性发作研究的新靶点。

To screen and analyze key genes by bioinformatics techniques to investigate the pathological mechanisms of acute asthma attack in children,the gene expression dataset(GSE103166)associated with acute asthma attack in children was downloaded from the GEO database.The differentially expressed genes(DEGs)between children with acute asthma attack and healthy children were screened using the R package tool,and GO analysis of DEG lists and annotation results from the KEGG were obtained using DAVID(version6.8),which were analyzed by STRING(version 11.0).Cytoscape and its plug-in MCODE were used to construct protein interaction networks and identify key genes.The results showed that a total of 78 DEGs were identified,including 49 up-regulated and 29 down-regulated genes,which were mainly enriched in biological processes such as nucleocytoplasmic transport and immune system process regulation,cellular components such as nuclear nucleosome and DNA packaging complex,and molecular functions such as Rho GTPase binding and ionotropic glutamate receptor binding.KEGG pathway was enriched in systemic lupus erythematosus and asthma signaling pathway.Among these DEGs,a gene module was screened out,which was mainly enriched in biological processes such as interferon-gamma-mediated signaling pathway,antigen processing and presentation of exogenous peptide antigen via MHC classⅡ,antigen processing and presentation of peptide antigen via MHC classⅡ,cellular components such as MHC classⅡprotein complex,lumenal side of endoplasmic reticulum membrane,integral component of lumenal side of endoplasmic reticulum membrane,and molecular functions such as MHC classⅡreceptor activity,peptide antigen binding,transmembrane signaling receptor activity.The KEGG pathway was mainly enriched in asthma,graft-versus-host disease,and allograft rejection pathways.The gene module contains five key genes,including HLA-DPB1,HLA-DQB1,HLA-DQB2,MT2A and KIF11.The above results showed that DEGs and key genes contribute to a better understanding of the pathological mechanisms of children with acute asthma attack.As the correlation of the three key genes HLA-DPB1,HLA-DQB1,and HLA-DQB2 with the disease has been validated by other studies,the two unconfirmed key genes MT2 A and KIF11 may be used as new targets for studying acute asthma attack in children.